DESCRIPTION: (Applicant's Abstract) The acute behavioral effects of cocaine are mediated, in part, by monoamine transmitters located in mesolimbic circuits. The presence of high concentrations of the serotonin (5HT) receptor subtypes, 5HT4 and 5HT6, in the nucleus accumbens and striatum suggests that 5HT systems may modulate the locomotor and discriminative stimulus properties of cocaine. The intent of the present studies is to assess this hypothesis by measuring the locomotor and discriminative stimulus effects of cocaine following either activation or blockade of the brain 5HT4 receptor with systemic administration of 5HT4 receptor ligands as well as following depletion of the brain 5HT6 receptor with intracranial infusion of specific antisense oligonucleotides.